Abstract 2880: Role of Akt isoforms in chemoresistance of endometrial carcinoma cells
Bibliographic record
Abstract
Abstract Akt (PKB) is a crucial survival kinase that is normally activated by a variety of growth factors. In tumours, its upstream regulation is affected by oncogenic events, which leads to the constitutive activation of the protein. Since studies have demonstrated that the three Akt isoforms exhibit different physiological functions, our hypothesis is that Akt isoforms may contribute differently in chemoresistance of endometrial carcinoma cells. The aim of this study is to determine the effect of a loss of function of each of Akt isoform in chemoresistant KLE endometrial carcinoma cells. In order to determine the specific role of each Akt isoform in cell survival/resistance to apoptosis and proliferation, we stably transfected KLE cells, which normally express Akt1, Akt2 and Akt3, with specific shRNA for each Akt isoform. We treated Akt isoform-specific transfectants for a period of 48 hour with different chemotherapeutics drugs and we performed western blot analysis for pro-apoptotic and anti-apoptotic factors. In this study, we have demonstrated that Akt1 and Akt2 downregulation sensitize KLE cells to cisplatin, doxorubicin and taxol. After treatment of KLE transfectants with all three drugs, we were able to see that activation pro-apoptotic factors such as cleaved caspase-3, -6 and -9 as well as cleaved PARP were induced. Moreover, the expression of anti-apoptotic factor XIAP was downregulated after drug treatment in these cells. Finally, Bcl-2 expression was inhibited after cisplatin treatment in Akt2 negative cells. We also performed MTT proliferation assay after a 72 hours treatment with chemotherapeutic drugs. Results gained from this study show that each Akt isoform is specifically implicated in cell survival. Akt1 and Akt2 shRNA clones were more sensitive to cisplatin, doxorubicin and taxol treatment. Akt3 shRNA clones were also more sensitive to cisplatin and doxorubicin but were less affected by taxol treatment. Our findings highlight the contribution of Akt isoforms in the molecular mechanisms that confer KLE cells resistance to chemotherapeutics drugs-induced apoptosis. According to our hypothesis, results show the differential implication of each Akt isoform in cell resistance to different chemotherapeutics drugs. We also showed that each isoform have a distinct impact on resistance to apoptosis induced by a given drug. Thus, the results confirm that Akt isoforms could be putative targets for therapy of endometrial cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2880. doi:10.1158/1538-7445.AM2011-2880
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".